ONCOLOGY LETTERS 9: 626-628, 2015
626
Extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor of the mediastinum: Significant response to chemoradiotherapy MIN LIU1, BAILONG LIU1, LIHUA DONG1, TAO HAN1 and LEI ZHANG2 Departments of 1Radiation Oncology and 2Radiology, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China Received May 22, 2014; Accepted November 21, 2014 DOI: 10.3892/ol.2014.2788 Abstract. Primary mediastinal extraskeletal Ewing's sarcoma (EES) is quite rare. To the best of our knowledge, only five cases have been reported. Given the paucity of data, there is consequently no optimal treatment strategy available. The current study presents the case of a 51‑year‑old female with unresectable EES of the posterior mediastinum. Chemoradiotherapy achieved near complete remission without severe side‑effects. The literature associated with EES is also reviewed. The present case highlights the possibility of the diagnosis of EES for a mediastinal mass. Chemoradiotherapy may be a good option for unresectable cases. In the future, large‑scale collaborative clinical trials should be initiated to provide an improved understanding of the characteristics of EES and the best treatment strategy. Introduction Extraskeletal Ewing's sarcoma (EES)/primitive neuroectodermal tumor (PNET) is a rare entity, accounting for 15% of all Ewing's sarcomas (1). The most common clinical manifestation of this disease is a rapidly growing, painful lump (2). Pathological, cytogenetic, immunohistochemical and molecular genetic analysis contribute to an accurate diagnosis (3). Multidisciplinary treatment modalities comprising extended resection, aggressive chemotherapy and local irradiation are recommended (4). At present, EES/PNET is viewed as a potentially curable disease (5). Primary mediastinal EES is extremely rare. The present study describes the case of a middle‑aged female with mediastinal EES who received sequential chemotherapy and radiotherapy and achieved a marked response. Written informed consent was obtained from the patient. Additionally,
Correspondence to: Dr Bailong Liu or Dr Lihua Dong, Department of Radiation Oncology, The First Hospital, Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, P.R. China E‑mail: [email protected] E‑mail: [email protected]
Key
words: extraskeletal chemoradiotherapy
Ewing's
sarcoma,
mediastinum,
the associated studies on EES are also reviewed. Further studies are required to establish the standard treatment strategy for EES. Written informed consent was obtained from the patient. Case report On December 25, 2012, a 51‑year‑old female presented with intermittent chest pain that had been apparent for one year. The physical examination was unremarkable. The patient's performance status was 1 according to an Eastern Cooperative Oncology Group (ECOG) evaluation (6). Laboratory investigations revealed a normal complete blood cell count, coagulation routine and serum biochemical profile. The thoracic computed tomography (CT) scan revealed a huge mass in the posterior mediastinum, with invasion of the esophagus, descending aorta and right pulmonary artery (Fig. 1A). On December 31, 2012, a biopsy of the mediastinal mass was performed by thoracoscopy, during which an irregular posterior mediastinal mass measuring ~8x8 cm was located under the arch of the azygos vein. The final pathology showed a malignancy of small round cells, which was consistent with an Ewing's sarcoma/PNET (Fig. 2A). The immunohistochemical results demonstrated a Ki‑67 of 20% (Fig. 2B), positivity for cluster of differentiation (CD)99 (Fig. 2C) and synaptophysin (Fig. 2D), partial positivity for CD56, neuron‑specific enolase and S‑100, and negativity for CD1a, Wilms tumor 1 protein, octamer‑binding transcription factor 3/4, vimentin, epithelial membrane antigen, cytokeratin (CK)5/6, desmin, thyroid transcription factor‑1, inhibin A, CD34, terminal deoxynucleotidyl transferase, CK and leukocyte common antigen. The following abdominal CT, brain magnetic resonance imaging and bone scan excluded the possibility of metastasis. The patient was administered four cycles of dacarbazine and pirarubicin chemotherapy. One cycle consisted of 300 mg dacarbazine on days 1‑5 and 40 mg pirarubicin on days 1‑2, for 21 days (patient's body surface area, ~1.6 m2). Following one cycle of chemotherapy, the tumor rapidly decreased in size (Fig. 1B) and the patient's discomfort disappeared. The thoracic CT revealed that the tumor became even smaller after three cycles compared with one cycle (Fig. 1C). Minimal residual tumor remained subsequent to four cycles of chemotherapy (Fig. 1D). Radiotherapy was then administered to the tumor bed at a total dose of 54 Gy/30 fractions over 42 days (between May 10, 2013, and June 21, 2013) and the recorded side‑effects, such as esophagitis and leukopenia, were mild.
LIU et al: EXTRASKELETAL EWING’S SARCOMA OF THE MEDIASTINUM
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Figure 1. Thoracic computed tomgraphy (CT) scan showing the lesion prior to treatment and during varying stages of treatment. (A) CT scan from December 25, 2012, showing a large mass in the posterior mediastinum. (B) Following one cycle of chemotherapy, the tumor was greatly reduced in size. (C) CT scan showing the smaller tumor following three cycles of chemotherapy. (D) Pre‑radiotherapy CT scan showing the residual tumor.
Figure 2. Pathological and immunohistochemical results. (A) The lesion was composed of primitive small round cells (H&E staining), with (B) a Ki‑67 of 20% and positivity for (C) cluster of differentiation 99 and (D) synaptophysin.
Discussion EES is a rare entity with high‑grade malignancy commonly involving the soft tissues of the trunk and extremities. The thoracic sites of EES include the chest wall, trachea, spinal epidural space, paraspinal area and mediastinum (7‑11). Primary mediastinal EES/PNET is extremely rare (1,12); to
the best of our knowledge, only five such cases have previously been reported (1,11‑14). The present case will therefore aid in expanding our understanding of this distinct neoplasm. EES often exhibits translocation of (11;22)(q24;q12) (3). CD99‑positive expression plays a crucial role in the diagnosis of EES (15). Tural et al reported indicators of poor overall survival, namely a primary tumor of >8 cm, a high level of lactic
628
ONCOLOGY LETTERS 9: 626-628, 2015
dehydrogenase, metastasis at the time of the first hospital visit, a poor response to chemotherapy, radiotherapy as the single method to improve local control and positive margins (16). For a long period of time, EES had been regarded as exhibiting no significant differences to osseous Ewing's sarcoma. A study by Applebaum et al (17) was the first to reveal that EES exhibited a different therapeutic response and clinical characteristics. The mean age of onset is older in EES, with a biphasic distribution to its peak age of onset: >35 and
626
Extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor of the mediastinum: Significant response to chemoradiotherapy MIN LIU1, BAILONG LIU1, LIHUA DONG1, TAO HAN1 and LEI ZHANG2 Departments of 1Radiation Oncology and 2Radiology, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China Received May 22, 2014; Accepted November 21, 2014 DOI: 10.3892/ol.2014.2788 Abstract. Primary mediastinal extraskeletal Ewing's sarcoma (EES) is quite rare. To the best of our knowledge, only five cases have been reported. Given the paucity of data, there is consequently no optimal treatment strategy available. The current study presents the case of a 51‑year‑old female with unresectable EES of the posterior mediastinum. Chemoradiotherapy achieved near complete remission without severe side‑effects. The literature associated with EES is also reviewed. The present case highlights the possibility of the diagnosis of EES for a mediastinal mass. Chemoradiotherapy may be a good option for unresectable cases. In the future, large‑scale collaborative clinical trials should be initiated to provide an improved understanding of the characteristics of EES and the best treatment strategy. Introduction Extraskeletal Ewing's sarcoma (EES)/primitive neuroectodermal tumor (PNET) is a rare entity, accounting for 15% of all Ewing's sarcomas (1). The most common clinical manifestation of this disease is a rapidly growing, painful lump (2). Pathological, cytogenetic, immunohistochemical and molecular genetic analysis contribute to an accurate diagnosis (3). Multidisciplinary treatment modalities comprising extended resection, aggressive chemotherapy and local irradiation are recommended (4). At present, EES/PNET is viewed as a potentially curable disease (5). Primary mediastinal EES is extremely rare. The present study describes the case of a middle‑aged female with mediastinal EES who received sequential chemotherapy and radiotherapy and achieved a marked response. Written informed consent was obtained from the patient. Additionally,
Correspondence to: Dr Bailong Liu or Dr Lihua Dong, Department of Radiation Oncology, The First Hospital, Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, P.R. China E‑mail: [email protected] E‑mail: [email protected]
Key
words: extraskeletal chemoradiotherapy
Ewing's
sarcoma,
mediastinum,
the associated studies on EES are also reviewed. Further studies are required to establish the standard treatment strategy for EES. Written informed consent was obtained from the patient. Case report On December 25, 2012, a 51‑year‑old female presented with intermittent chest pain that had been apparent for one year. The physical examination was unremarkable. The patient's performance status was 1 according to an Eastern Cooperative Oncology Group (ECOG) evaluation (6). Laboratory investigations revealed a normal complete blood cell count, coagulation routine and serum biochemical profile. The thoracic computed tomography (CT) scan revealed a huge mass in the posterior mediastinum, with invasion of the esophagus, descending aorta and right pulmonary artery (Fig. 1A). On December 31, 2012, a biopsy of the mediastinal mass was performed by thoracoscopy, during which an irregular posterior mediastinal mass measuring ~8x8 cm was located under the arch of the azygos vein. The final pathology showed a malignancy of small round cells, which was consistent with an Ewing's sarcoma/PNET (Fig. 2A). The immunohistochemical results demonstrated a Ki‑67 of 20% (Fig. 2B), positivity for cluster of differentiation (CD)99 (Fig. 2C) and synaptophysin (Fig. 2D), partial positivity for CD56, neuron‑specific enolase and S‑100, and negativity for CD1a, Wilms tumor 1 protein, octamer‑binding transcription factor 3/4, vimentin, epithelial membrane antigen, cytokeratin (CK)5/6, desmin, thyroid transcription factor‑1, inhibin A, CD34, terminal deoxynucleotidyl transferase, CK and leukocyte common antigen. The following abdominal CT, brain magnetic resonance imaging and bone scan excluded the possibility of metastasis. The patient was administered four cycles of dacarbazine and pirarubicin chemotherapy. One cycle consisted of 300 mg dacarbazine on days 1‑5 and 40 mg pirarubicin on days 1‑2, for 21 days (patient's body surface area, ~1.6 m2). Following one cycle of chemotherapy, the tumor rapidly decreased in size (Fig. 1B) and the patient's discomfort disappeared. The thoracic CT revealed that the tumor became even smaller after three cycles compared with one cycle (Fig. 1C). Minimal residual tumor remained subsequent to four cycles of chemotherapy (Fig. 1D). Radiotherapy was then administered to the tumor bed at a total dose of 54 Gy/30 fractions over 42 days (between May 10, 2013, and June 21, 2013) and the recorded side‑effects, such as esophagitis and leukopenia, were mild.
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Figure 1. Thoracic computed tomgraphy (CT) scan showing the lesion prior to treatment and during varying stages of treatment. (A) CT scan from December 25, 2012, showing a large mass in the posterior mediastinum. (B) Following one cycle of chemotherapy, the tumor was greatly reduced in size. (C) CT scan showing the smaller tumor following three cycles of chemotherapy. (D) Pre‑radiotherapy CT scan showing the residual tumor.
Figure 2. Pathological and immunohistochemical results. (A) The lesion was composed of primitive small round cells (H&E staining), with (B) a Ki‑67 of 20% and positivity for (C) cluster of differentiation 99 and (D) synaptophysin.
Discussion EES is a rare entity with high‑grade malignancy commonly involving the soft tissues of the trunk and extremities. The thoracic sites of EES include the chest wall, trachea, spinal epidural space, paraspinal area and mediastinum (7‑11). Primary mediastinal EES/PNET is extremely rare (1,12); to
the best of our knowledge, only five such cases have previously been reported (1,11‑14). The present case will therefore aid in expanding our understanding of this distinct neoplasm. EES often exhibits translocation of (11;22)(q24;q12) (3). CD99‑positive expression plays a crucial role in the diagnosis of EES (15). Tural et al reported indicators of poor overall survival, namely a primary tumor of >8 cm, a high level of lactic
628
ONCOLOGY LETTERS 9: 626-628, 2015
dehydrogenase, metastasis at the time of the first hospital visit, a poor response to chemotherapy, radiotherapy as the single method to improve local control and positive margins (16). For a long period of time, EES had been regarded as exhibiting no significant differences to osseous Ewing's sarcoma. A study by Applebaum et al (17) was the first to reveal that EES exhibited a different therapeutic response and clinical characteristics. The mean age of onset is older in EES, with a biphasic distribution to its peak age of onset: >35 and
